Hepatic CYP1A2 Activity in Adolescents with and without Obesity Assessed by the Urinary Paraxanthine‐to‐Caffeine Metabolic Ratio: A Pharmacokinetic Study

Obesity-related metabolic and hepatic alterations may influence drug metabolism via cytochrome P450 enzymes. While adult studies suggest altered CYP1A2 activity in obesity, data in pediatric populations remain limited and inconclusive. The objective was to assess the in vivo CYP1A2 phenotype in adolescents aged 11-18 years with and without obesity, and to explore sex-based differences in enzyme activity within this age group. In this open-label pharmacokinetic study, which is a part of the CYTONOX study, 65 adolescents aged 11-18 years were included, comprising 30 individuals with obesity and 35 without obesity, recruited based on feasibility. The CYP1A2 phenotype was assessed using urinary paraxanthine/caffeine metabolic ratios following caffeine exposure. Hepatic fat content was measured via magnetic resonance spectroscopy. The study received approval from the Danish Health Authorities (EudraCT: 2014-004554-34) and the Regional Ethical Committee of Zealand (SJ-455). Despite metabolic differences and increased hepatic fat in the obese group, the CYP1A2 phenotype did not differ significantly between obese and non-obese adolescents (mean log10 urinary metabolic ratio: 0.82 vs 0.80; P = .93). No sex-based differences were observed. Obesity in adolescents does not appear to significantly impact CYP1A2 phenotype assessed by urinary metabolic ratio, in contrast to selected studies in adults. These findings suggest preserved CYP1A2 function during adolescence despite metabolic and hepatic changes. Further longitudinal studies are needed to elucidate the age-related progression of hepatic enzyme activity in context of obesity.